Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt

  1. Péter Lőrincz  Is a corresponding author
  2. Lili Anna Kenéz
  3. Sarolta Tóth
  4. Viktória Kiss
  5. Ágnes Varga
  6. Tamás Csizmadia
  7. Zsófia Simon-Vecsei
  8. Gábor Juhász  Is a corresponding author
  1. Eötvös Loránd University, Hungary
  2. Hungarian Academy of Sciences, Hungary

Abstract

Two related multisubunit tethering complexes promote endolysosomal trafficking in all eukaryotes: Rab5-binding CORVET that was suggested to transform into Rab7-binding HOPS. We have previously identified miniCORVET, containing Drosophila Vps8 and three shared core proteins, which is required for endosome maturation upstream of HOPS in highly endocytic cells (Lorincz et al., 2016a). Here we show that Vps8 overexpression inhibits HOPS-dependent trafficking routes including late endosome maturation, autophagosome-lysosome fusion, crinophagy and lysosome-related organelle formation. Mechanistically, Vps8 overexpression abolishes the late endosomal localization of HOPS-specific Vps41/Lt and prevents HOPS assembly. Proper ratio of Vps8 to Vps41 is thus critical because Vps8 negatively regulates HOPS by outcompeting Vps41. Endosomal recruitment of miniCORVET- or HOPS-specific subunits requires proper complex assembly, and Vps8/miniCORVET is dispensable for autophagy, crinophagy and lysosomal biogenesis. These data together indicate the recruitment of these complexes to target membranes independent of each other in Drosophila, rather than their transformation during vesicle maturation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Péter Lőrincz

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    For correspondence
    concrete05@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7374-667X
  2. Lili Anna Kenéz

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Sarolta Tóth

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Viktória Kiss

    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Ágnes Varga

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  6. Tamás Csizmadia

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  7. Zsófia Simon-Vecsei

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7909-4895
  8. Gábor Juhász

    Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary
    For correspondence
    szmrt@elte.hu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8548-8874

Funding

Magyar Tudományos Akadémia (LP-2014/2)

  • Gábor Juhász

Ministry of Human Capacities of Hungary (ÚNKP-18-4-ELTE-409)

  • Zsófia Simon-Vecsei

Magyar Tudományos Akadémia (PPD-222/2018)

  • Péter Lőrincz

Magyar Tudományos Akadémia (BO/00652/17)

  • Zsófia Simon-Vecsei

National Research, Development and Innovation Office of Hungary (GINOP-2.3.2-15-2016-00006)

  • Gábor Juhász

National Research, Development and Innovation Office of Hungary (GINOP-2.3.2-15-2016-00032)

  • Gábor Juhász

National Research, Development and Innovation Office of Hungary (K119842)

  • Gábor Juhász

National Research, Development and Innovation Office of Hungary (KKP129797)

  • Gábor Juhász

National Research, Development and Innovation Office of Hungary (PD124594)

  • Zsófia Simon-Vecsei

Ministry of Human Capacities of Hungary (ÚNKP-18-2-II-ELTE-32)

  • Lili Anna Kenéz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Alexey J Merz, University of Washington School of Medicine, United States

Version history

  1. Received: January 31, 2019
  2. Accepted: June 13, 2019
  3. Accepted Manuscript published: June 13, 2019 (version 1)
  4. Version of Record published: June 25, 2019 (version 2)

Copyright

© 2019, Lőrincz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Péter Lőrincz
  2. Lili Anna Kenéz
  3. Sarolta Tóth
  4. Viktória Kiss
  5. Ágnes Varga
  6. Tamás Csizmadia
  7. Zsófia Simon-Vecsei
  8. Gábor Juhász
(2019)
Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt
eLife 8:e45631.
https://doi.org/10.7554/eLife.45631

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